The objective of this research project is to identify and characterize cell surface glycoproteins of mouse lymphocytes with a long-term goal of understanding lymphocyte differentiation and function. Work has continued on preparing monoclonal antibodies against cell surface molecules that may be of functional significance, and a large number of antibodies against a murine natural killer cell line derived by Dr. G. Dennert (Salk Institute) have been obtained. Preliminary testing has been completed and several antibodies have been identified that block cytolysis by natural killer cells. However, the major emphasis has been to develop the molecular biological techniques necessary to obtain the genes encoding lymphocyte cell surface molecules. We have shown that cotransformation of mouse L cells with the herpes thymidine kinase gene and high molecular weight DNA from lymphoid cells in conjunction with fluorescence-activated cell sorting is a feasible method of identifying and isolating genes for cell surface molecules defined by monoclonal antibodies. We intend to use this approach to study the molecular biology of a variety of lymphocyte cell surface molecules with known function.